The taste and odour thresholds for chlorine in distilled water are 5 and 2 mg/litre,respectively. In air, chlorine has a pungent and disagreeable odour (2).

Major uses

Large amounts of chlorine are produced for use as disinfectants and bleach for both domesticand industrial purposes, and it is also widely used to disinfect drinking-water and swimmingpoolwater and to control bacteria and odours in the food industry (3,4).

Environmental fate

In water, chlorine reacts to form hypochlorous acid and hypochlorites. All three species existin equilibrium with each other, the relative amounts varying with the pH. In dilute solutionsand at pH levels above 4.0, very little molecular chlorine exists in solution. Theconcentrations of hypochlorous acid and the hypochlorite ion are approximately equal at pH7.5 and 25 °C. Chlorine can react with ammonia or amines in water to form chloramines(4,5).

ANALYTICAL METHODS

A colorimetric method can be used to determine free chlorine in water at concentrations of0.1–10 mg/litre. Other methods allow for the determination of free chlorine, chloramines,other chlorine species, and total available chlorine, and are suitable for total chlorineconcentrations up to 5 mg/litre. The minimum detectable concentration of chlorine is about0.02 mg/litre (6).

ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

AirA mean ambient air level of 1 mg/m3 was reported for chlorine (7).

2WaterChlorine is present in most disinfected drinking-water at concentrations of 0.2–1 mg/litre (3).

Estimated total exposure and relative contribution of drinking-waterThe major routes of exposure to chlorine are through drinking-water, food, and contact withitems either bleached or disinfected with it.

KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS

Most studies on the pharmacokinetics of chlorine, hypochlorous acid, or hypochloritesemploy reactive 36Cl-labelled compounds and probably reflect the fate of the chloride ion orother reaction products generated from the parent molecules. In rats, hypochlorous acid wasreadily absorbed through the gastrointestinal tract, distribution being highest in the plasma;smaller amounts were found in bone marrow, kidney, testes, lung, skin, duodenum, spleen,liver, and bone (9,10). In vivo, sodium hypochlorite was metabolized to trichloroethanoicacid, dichloroethanoic acid, chloroform, and dichloroacetonitrile (11). Hypochlorous acidadministered to rats was excreted primarily in the urine and faeces, mostly in the form ofchloride ion (10). None was excreted in expired air (9).

EFFECTS ON LABORATORY ANIMALS AND IN VITRO TEST SYSTEMS

Acute exposureCalcium hypochlorite has an oral LD50 in the rat of 850 mg/kg of body weight (2).

Short-term exposure

No consistent effects on organ weights or histopathology of tissues were noted in Sprague-Dawley rats (10 per sex per dose) given chlorine in drinking-water at 0, 25, 50, 100, 175, or200 mg/litre (males: 0, 2, 7.5, 12.8, or 16.7 mg/kg of body weight per day; females: 0, 3.5,12.6, 19.5, or 24.9 mg/kg of body weight per day) for 90 days (12) or in rats fed flourcontaining 1257 or 2506 mg of chlorine per kg (62.5 or 125 mg/kg of body weight per day)for 28 days (13).Enhanced weight gain was observed in all male rats (10 per dose) given drinking-watercontaining chlorine at 0, 20, 40, or 80 mg/litre (0, 4.1, 8.1, or 15.7 mg/kg of body weight perday) for 6 weeks (14). The results of a 4-week study in which female C57BL/6N mice weregiven hyperchlorinated tapwater (4.8–5.8 mg/kg of body weight per day) suggested anadverse effect on the macrophage defence mechanisms of mice. The LOAEL in this studywas 4.8 mg/kg of body weight per day (15).In a study in which male CR-1:CD-1 mice (30 per dose) received chlorinated drinking-water(0.02, 0.2, 2.9, or 5.8 mg/kg of body weight per day) for 120 days, none of the mice showedevidence of a statistically significant change in humoral or cell-mediated immune response. ANOAEL of 5.8 mg/kg of body weight per day was identified (16).3

Long-term exposure

F344 rats (50 per sex per dose) were administered sodium hypochlorite in drinking-water(males: 0.05% or 0.1%, 75 or 150 mg/kg of body weight per day; females: 0.1% or 0.2%, 150or 300 mg/kg of body weight per day) for 2 years. Effects included a dose-related depressionin body weight gain in all groups, depressed liver, brain, and heart weights in males given a0.05% dose, decreased salivary gland weights in both female groups, and decreased kidneyweights in females given 0.2% (17).In a 2-year bioassay, F344 rats and B6C3F1 mice were given chlorine in drinking-water atlevels of up to 275 mg/litre (up to 24 mg/kg of body weight per day for male rats and malemice, 15 mg/kg of body weight per day for female rats, and 22 mg/kg of body weight per dayfor female mice). There was a dose-related decrease in water consumption for both mice andrats. No effects on body weight or survival were observed in any of the treated animals (18).Wistar rats were fed cake prepared from flour treated with 1250 or 2500 mg of chlorine perkg (males: 12.8 or 25.3 mg/kg of body weight per day; females: 17.0 or 35.0 mg/kg of bodyweight per day) for 104 weeks. A dose-related reduction in spleen weight was seen infemales, and dose-related haematological effects were observed in both sexes. A LOAEL of12.8 mg/kg of body weight per day was identified in this study (19).

Reproductive effects, embryotoxicity, and teratogenicity

C3H/HeJ and C57BL/6J mice administered drinking-water containing 10 mg of residualchlorine per litre (1.9 mg/kg of body weight per day) for 6 months showed no adversereproductive effects (20). In a seven-generation study in which rats were given drinking-waterchlorinated at 100 mg/litre (10 mg/kg of body weight per day), no treatment-related effects onfertility were found (21).Oral administration of hypochlorite ion or hypochlorous acid at 100, 200, or 400 mg ofchlorine per litre (1.6, 4.0, or 8.0 mg/kg of body weight per day) resulted, in the case ofhypochlorite, in dose-related increases in the amount of sperm-head abnormalities in maleB6C3F1 mice. A NOAEL of 8.0 mg/kg of body weight per day was identified forhypochlorous acid and a LOAEL of 1.6 mg/kg of body weight per day for hypochlorite ion(22).

Mutagenicity and related end-points

Sodium hypochlorite has been found to be mutagenic in Salmonella typhimurium TA1530and TA100 but not TA1538 (23,24). Calcium and sodium hypochlorite both producedchromosomal aberrations in Chinese hamster fibroblast cells without metabolic activation(24). Hypochlorite ion and hypochlorous acid were negative in the in vivo erythrocytemicronucleus assay and in bone marrow aberration studies (22).

Carcinogenicity

F344 rats (50 per sex per dose) were given sodium hypochlorite in drinking-water (males:0.05% or 0.1%, 75 or 150 mg/kg of body weight per day; females: 0.1% or 0.2%, 150 or 300mg/kg of body weight per day) for 2 years. Experimental groups did not differ from controlswith respect to the total tumour incidences or mean survival times, and most of the tumoursfound were of types that commonly occur spontaneously in F344 rats. The authors concludedthat sodium hypochlorite was not carcinogenic in rats (17).In a seven-generation toxicity study, the incidence of malignant tumours in rats consumingdrinking-water with a free chlorine level of 100 mg/litre (10 mg/kg of body weight per day)4did not differ from that in controls (21). The incidence of tumours in treated animals was notsignificantly elevated in F344 rats and B6C3F1 mice (50 per sex per dose) given solutions ofsodium hypochlorite (70 or 140 mg/kg of body weight per day for male rats, 95 or 190 mg/kgof body weight per day for female rats, 84 or 140 mg/kg of body weight per day for male andfemale mice) in their drinking-water for 103–104 weeks (25).In a 2-year bioassay, F344 rats and B6C3F1 mice were given chlorine in drinking-water atlevels of 0, 70, 140, or 275 mg/litre (8, 13, or 24 mg/kg of body weight per day for male rats;5, 7, or 15 mg/kg of body weight per day for female rats; 8, 15, or 24 mg/kg of body weightper day for male mice; and 1, 13, or 22 mg/kg of body weight per day for female mice).Although there was a marginal increase in mononuclear-cell leukaemia in the groups offemale rats given 140 and 275 mg/litre, it was considered to be equivocal evidence ofcarcinogenic activity because the incidence was significantly elevated compared with controlsonly for the middle dose and the incidence of leukaemia in the concurrent controls was lowerthan the mean in historical controls (18).

EFFECTS ON HUMANS

Exposure to chlorine, hypochlorous acid, and hypochlorite ion through ingestion of householdbleach occurs most commonly in children. Intake of a small quantity of bleach generallyresults in irritation of the oesophagus, a burning sensation in the mouth and throat, andspontaneous vomiting. In these cases, it is not clear whether it is the sodium hypochlorite orthe extremely caustic nature of the bleach that causes the tissue injury.The effects of heavily chlorinated water on human populations exposed for varying periodswere summarized in a report that was essentially anecdotal in character and did not describein detail the health effects observed (26). In a study on the effects of progressively increasingchlorine doses (0, 0.001, 0.014, 0.071, 0.14, 0.26, or 0.34 mg/kg of body weight) on healthymale volunteers (10 per dose), there was an absence of adverse, physiologically significanttoxicological effects in all of the study groups (27). It has been reported that asthma can betriggered by exposure to chlorinated water (28). Episodes of dermatitis have also beenassociated with exposure to chlorine and hypochlorite (29,30).In a study of 46 communities in central Wisconsin where chlorine levels in water ranged from0.2 to 1 mg/litre, serum cholesterol and low-density lipoprotein levels were higher incommunities using chlorinated water. Levels of high-density lipoprotein (HDL) and thecholesterol/HDL ratio were significantly elevated in relation to the level of calcium in thedrinking-water, but only in communities using chlorinated water. The authors speculated thatchlorine and calcium in drinking-water may interact in some way that affects lipid levels (31)An increased risk of bladder cancer appeared to be associated with the consumption ofchlorinated tapwater in a population-based, case–control study of adults consumingchlorinated or non-chlorinated water for half of their lifetimes (32).

GUIDELINE VALUE

In humans and animals exposed to chlorine in drinking-water, specific adverse treatmentrelatedeffects have not been observed. IARC has concluded that hypochlorites are notclassifiable as to their carcinogenicity to humans (Group 3) (17).The guideline value for free chlorine in drinking-water is derived from a NOAEL of 15 mg/kgof body weight per day, based on the absence of toxicity in rodents that received chlorine ashypochlorite in drinking-water for up to 2 years (18). Application of an uncertainty factor of100 (for inter- and intraspecies variation) to this NOAEL gives a TDI of 150 μg/kg of bodyweight. With an allocation of 100% of the TDI to drinking-water, the guideline value is 55mg/litre (rounded figure). It should be noted, however, that this value is conservative, as noadverse effect level was identified in this study. Most individuals are able to taste chlorine orits by-products (e.g. chloramines) at concentrations below 5 mg/litre, and some at levels aslow as 0.3 mg/litre.